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Increasing evidence implicates aberrant immune activation and vascular injury in PE pathogenesis, but the upstream signals and cellular mechanisms remain incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We integrated transcriptomic profiling, maternal serum cytokine analysis, and placental immunohistochemistry to identify dysregulated chemokines. Human and murine trophoblasts were stimulated under hypoxia or LPS challenge to assess IL-8\/CXCL1 production. Functional assays of NET formation and endothelial apoptosis were conducted in trophoblast\u2013neutrophil\u2013endothelium co-culture systems. Finally, we tested the therapeutic effects of neutralizing anti-CXCL1 antibody or the CXCR1\/2 inhibitor SX682 in LPS-induced murine models of PE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found that IL-8 was markedly elevated in PE patients and correlated with disease severity. Hypoxia- or LPS-stimulated trophoblasts secreted abundant IL-8\/CXCL1, which recruited and activated neutrophils to undergo NETosis. NETs directly induced endothelial mitochondrial dysfunction and apoptosis, resulting in vascular injury. Pharmacological blockade of IL-8 signaling, either by CXCL1 neutralization or CXCR1\/2 inhibition, significantly ameliorated hypertension, proteinuria, and fetal growth restriction in murine PE models, without altering placental weight or gross morphology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings define a trophoblast\u2013neutrophil\u2013endothelium axis in which IL-8\u2013driven NETosis exacerbates vascular pathology in PE. Targeting IL-8\/CXCL1-CXCR1\/2 signaling interrupts this pathogenic circuit, restores endothelial function, and improves maternal and fetal outcomes. These results highlight IL-8 signaling as a promising therapeutic target for PE.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-026-08084-3","type":"journal-article","created":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T16:28:25Z","timestamp":1775320105000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["IL-8\u2013driven neutrophil NETosis triggers endothelial apoptosis and exacerbates preeclampsia"],"prefix":"10.1186","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9592-1800","authenticated-orcid":false,"given":"Wushan","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinlin","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengchun","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoxia","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,4]]},"reference":[{"issue":"10297","key":"8084_CR1","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/S0140-6736(20)32335-7","volume":"398","author":"LC Chappell","year":"2021","unstructured":"Chappell LC, Cluver CA, Kingdom J, Tong S, Pre-eclampsia. 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